Table 1.
Synthesis of 2,4-diamino-5-aryl-6-substituted pyrimidine derivatives 16a-p via Suzuki reactions.
| Entry | R2 | R3 | Product | Yield c (%) | Clog P d |
|---|---|---|---|---|---|
| 1 | -CH2OCH3 (14a) | 4-OCF3 | 16a a | 74 | 2.99 |
| 2 | -CH2OCH3 (14a) | 3-OCF3 | 16b a | 74 | 2.99 |
| 3 | -CH2OCH3 (14a) | 3-CH2OCH2CF3 | 16c a | 70 | 2.29 |
| 4 | -CH2OCH3 (14a) | 3-CH3-5-CH3-4-SO2NHOCH3 | 16d a | 73 | 1.19 |
| 5 | -CH2OCH3 (14a) |  |
16e a | 70 | 3.59 |
| 6 | -CH2CH2OCH3 (14b) | 4-OCF3 | 16f a | 75 | 3.37 |
| 7 | -CH2CH2OCH3 (14b) | 3-OCF3 | 16g a | 94 | 3.37 |
| 8 |
 (14c) |
4-OCF3 | 16h a | 87 | 2.81 |
| 9 |
(14c) |
3-OCF3 | 16i a | 73 | 2.81 |
| 10 |
(14c) |
3-CH2OCH2CF3 | 16j a | 91 | 2.11 |
| 11 |
(14c) |
3-CH3-5-CH3-4-SO2NHOCH3 | 16k a | 72 | 1.01 |
| 12 |
(14c) |
|
16l a | 99 | 3.42 |
| 13 |
 (14d) |
4-OCF3 | 16m a | 91 | 3.56 |
| 14 |
(14d) |
3-OCF3 | 16n a | 91 | 3.56 |
| 15 |
(14d) |
4-COOCH3 | 16o b | 68 | 2.39 |
| 16 |
(14d) |
3-COOCH3 | 16p b | 51 | 2.39 |
Reaction Conditions: a Pd(dbpf)Cl2 (0.02 mmol) and K2CO3 in EtOH/toluene/H2O at 90 °C for 24 h; b Pd(dbpf)Cl2 (0.02 mmol) and K2CO3 in THF/H2O at 70 °C for 20 h in sealed tube; c Isolated yields; d Calculated using ChemBioDraw (PerkinElmer, Waltham, MA, USA) 12.0.